Major Depressive Disorder (MDD) is among the most prevalent and devastating of all psychiatric disorders, and is the single most burdensome disease worldwide. Consequently, it is imperative that we identify and examine the effects of altering mechanisms involved in the maintenance of MDD. In this context, investigators have documented that difficulty removing negative information from working memory is a core cognitive feature of MDD. Importantly, this cognitive difficulty is implicated in the persistence o both depressive symptoms and rumination, a style of thinking that hinders recovery from stress and exacerbates negative affect. To date, research linking difficulty removing negative information from working memory with rumination, the persistence of negative affect, and stress recovery in MDD has been limited by the use of correlational methodologies. Importantly, the Cognitive Bias Modification (CBM) literature underscores the viability of manipulating cognitive processes both to test causal relations and to identify mechanisms involved in the onset and maintenance of disorders. Therefore, a major aim of the proposed study is to build on established CBM methods to improve depressed individuals' ability to remove negative information (RNI) from working memory. We propose to examine the cognitive, affective, and biological effects of RNI training (Aim 1). In addition, we also propose to examine the neural mechanisms that underlie the beneficial effects of RNI training (Aim 2). To achieve these aims, 50 participants diagnosed with MDD will be assigned to receive either Real or Sham RNI training. All participants will complete pre-training laboratory-based and neuroimaging sessions, six at-home Real or Sham RNI training sessions, post-training laboratory-based and neuroimaging sessions, and a three-month follow-up assessment. We expect that, compared to Sham RNI training, Real RNI training will a) improve depressed participants' ability to remove negative information from working memory from pre- to post-training; b) decrease levels of rumination and depressive symptoms; and c) improve subsequent emotional and biological stress recovery. We further expect that RNI training will achieve its beneficial effects by decreasing brain activation from pre- to post-training in regions that subserve cognitive effort (dorsal anterior cingulate, posterior parietal lobe, and insular cortex), and by decreasing functional connectivity in regions posited to underlie rumination (subgenual anterior cingulate cortex and medial prefrontal cortex). The results of this study will increase our understanding of the relations among biases in working memory, rumination, and depressive symptoms, and will help to identify and elucidate specific mechanisms that contribute to the onset and maintenance of MDD.